Renal denervation (RDN) has been developed to reduce blood pressure (BP) using a percutaneous catheter. Radiofrequency, ultrasound, and alcohol-based devices have been primarily tested in several randomized trials [1,2,3]. Based on these results, the FDA approved radiofrequency and ultrasound-based RDN as adjunctive treatment options when lifestyle changes and medication have not resulted in adequate blood pressure control as of November 2024. Currently, the target of RDN is resistant and uncontrolled hypertension. The safety of RDN has been consistent in most trials, with no safety concerns related to the procedure. However, the efficacy of RDN is not consistent. Some trials have failed to show the superiority of RDN compared to sham procedures, mainly due to the strong antihypertensive effect of the sham procedure [4, 5]. When the reduction of blood pressure is focused on the antihypertensive effect of RDN, it significantly reduces BP compared to baseline in all trials, regardless of antihypertensive medication therapy. RDN is thought to have a class effect of reducing BP.

In this issue, Ogoyama et al. evaluated the effects of RDN on BP using a meta-analysis of randomized sham-controlled trials involving 2222 patients in 14 randomized trials [6]. They assessed several BP measurements after RDN procedures. Interestingly, RDN significantly reduced all BP measurements, such as 24-hour ambulatory systolic BP, 24-hour ambulatory diastolic BP, office systolic BP, office diastolic BP, daytime systolic BP, daytime diastolic BP, nighttime systolic BP, nighttime diastolic BP, home systolic BP, and home diastolic BP. The efficacy of RDN is further robust in this meta-analysis. The topic of interest moves on to the next step (see Fig. 1).

Fig. 1
figure 1

Topic of interest in the field of RDN

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The current topic of interest is no longer efficacy and safety. Durability, relevance to clinical outcomes, cost-effectiveness, identification of responders, procedure guidance, and expanding indications are the main topics in the field of RDN.

1. Sympathetic nerve regeneration counteracts the effect of RDN, raising concerns about the durability of RDN’s effect. Recent long-term follow-up studies after RDN procedures have been published, indicating that the effect of RDN may persist for 3 years in some meta-analyses and 9 to 10 years in some registries [7]. However, the sample size is too small to draw definitive conclusions.

2. The magnitude of BP reduction was in the single digits (3–5 mmHg) in various BP parameters in this meta-analysis. Although this BP reduction theoretically impacts clinical outcomes, there is no randomized study showing that RDN is associated with better clinical outcomes compared to antihypertensive medications or sham procedures. In the global SYMPLICITY registry, the relative risk of cardiovascular events is estimated, with RDN associated with a significant reduction in major adverse cardiovascular events (MACE) and stroke rates at 3 years [8].

3. The cost-effectiveness of RDN has also been evaluated in some studies. The incremental cost-effective ratio meets the cost-effectiveness threshold per quality-adjusted life years in the UK [9]. Antihypertensive drugs are used to decrease BP over a lifelong period. The cost-effectiveness of RDN alongside antihypertensive medication might offer advantages, especially in young hypertensive patients.

4. The identification of responders to RDN is at the center of attention in the field. RDN is an invasive therapy, and identifying responders before the procedure could be critical for daily clinical practice. Many sub-studies aim to identify responders, with factors such as orthostatic hypertension, heart rate, plasma renin activity, arterial stiffness, and aortic pulse wave velocity seeming to be associated with responders [2, 10, 11]. However, whether the combination of these factors is more relevant to identifying RDN responders is currently unknown.

5. The effect of RDN does not appear immediately after the procedure. Therefore, whether substantial denervation has been achieved or not is not judged during the procedure. To overcome this limitation, several approaches have been developed. Renal artery spots associated with an increase in systolic BP are mapped using electronic stimulation catheters, and these hot spots are then ablated [12]. Another approach involves trans-vascular pacing of aorticorenal ganglia, which generally leads to renal artery spasm [13]. After substantial renal denervation, this response is not observed. This procedure might be useful for determining the end of the procedure.

6. RDN reduces sympathetic nerve activity, making it theoretically useful for treating patients with high sympathetic nerve activity. RDN might be effective in patients with sleep apnea, heart failure, atrial fibrillation, ventricular tachycardia, diabetes, or chronic kidney disease. Some reports show that RDN reduces the recurrence of atrial fibrillation after ablation [14]. Additionally, improvements in NYHA classification and decreases in NT-proBNP levels have been observed in patients with heart failure with preserved left ventricular ejection fraction [15].

Renal denervation has been approved as a treatment for resistant and uncontrolled hypertension in daily clinical use in the EU, USA, and many other countries. The preparation of multidisciplinary Hypertension Renal Denervation Treatment (HDRT) teams consisting of specialists in hypertension, cardiovascular intervention, and cardiology is warranted to use this new technology in real-world practice. Additionally, national databases are necessary to address the unresolved topics of RDN.